Dimethylformamide → HCID 178432445, compound

HRID 1875144Notes

Reaction equation

HRID 1875144 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:23])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Br:24][C:25]1[N:26]=[C:27]([CH3:33])[NH:28][C:29]=1[C:30]([OH:32])=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.CN([CH:70]=[O:71])C>CCOC(C)=O>[F:20][C:19]([F:22])([F:21])[C:70]([OH:71])=[O:31].[Br:24][C:25]1[N:26]=[C:27]([CH3:33])[NH:28][C:29]=1[C:30]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:23])=[O:32]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684835233-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrileHCID 1784324484-bromo-2-methyl-1H-imidazole-5-carboxylic acid

Product 1

HCID 178432445HCID 178432445, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrile (33.6 mg, 0.098 mmol), 4-bromo-2-methyl-1H-imidazole-5-carboxylic acid (20 mg, 0.098 mmol) and HATU (37.1 mg, 0.098 mmol) in DMF (5 ml) was added diisopropylethyl amine (0.034 ml, 0.195 mmol) and the mixture was stirred for 20 minutes at rt. The mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via reverse phase HPLC to give 4-bromo-N-[(4-chloro-3-{[3-cyano-5-(trifluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-2-methyl-1H-imidazole-5-carboxamide trifluoroacetate (15.0 mg, 0.023 mmol, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.23 (t, 1H), 8.11 (s, 1H), 7.79 (s, 1H), 7.74 (s, 1H), 7.50 (d, 1H), 7.36 (t, 1H), 4.49 (d, 2H), 2.26 (s, 3H). LC-MS (ES+) m/z 531.10, [M+H].

Workup

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-f6aba75503b14493b119aeb094e02403
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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